Efficient Atmospheric Pressure Interface for Mass Spectrometers and Method

ABSTRACT

An interface for atmospheric pressure ionization sources has an ion transfer tube with a plurality of passageways through a sidewall such that background gas can be pumped away before it reaches an exit end of the ion transfer tube. A flow of the background gas out the exit end is reduced, and a proportion of laminar flow in the ion transfer tube may be increased. Pressure in the ion transfer tube is also reduced and desolvation is increased. In one embodiment, an enclosure surrounds an inner tube of the ion transfer tube within a first vacuum chamber such that the enclosure provides a reduced pressure region within the first vacuum chamber. Overall, transport efficiency is increased.

This application claims priority to a provisional U.S. patentapplication Ser. No. 60/857,737 by Alexander A. Makarov et al., entitled“ION TRANSFER TUBE WITH SPATIALLY ALTERNATING DC FIELDS”, filed Nov. 7,2006, the disclosure of which is hereby incorporated herein byreference.

FIELD OF THE INVENTION

This application is directed to ion inlet sections of massspectrometers, ion transfer tube assemblies, ion transfer tubes, andmethods of transporting ions from an atmospheric pressure ion sourceinto a vacuum chamber of a mass spectrometer.

BACKGROUND OF THE INVENTION

Various approaches have been undertaken to increase desolvation andotherwise increase the number of ions introduced into the ion optics ofa mass spectrometer from an atmospheric pressure ion source. One typicalpractice is to heat a capillary tube to increase desolvation of sampleliquid droplets and to reduce the size of the droplets from electrosprayionization or chemical ionization sources, for example. U.S. Pat. No.5,245,186 to Chait et al. teaches heating the capillary tube with awire. U.S. Pat. No. 4,935,624 to Henion et al. teaches controlledheating of a capillary tube. Others have utilized a counter-flow ofheated gas to increase desolvation prior to entry of the spray into thecapillary tube.

U.S. Pat. No. 4,977,320 to Chowdhury et al. and others have relied uponthe strong flow of gas that accompanies the sample spray through thecapillary tube from an atmospheric pressure region into the vacuumregion to help focus the droplets toward a center of the capillary tube.U.S. Pat. No. 5,157,260 to Mylchreest et al. teaches use of tube lensesat an exit end of the capillary tube for focusing ions. Others haveutilized electrodes at various locations to focus and/or urge ionstoward an orifice of a skimmer or other ion optical element to causeions to enter lower pressure regions of mass spectrometers.

Various techniques for alignment and positioning of the sample spray,capillary tube, and skimmer have been implemented to maximize the numberof ions from the source that are actually received into the ion opticsof mass spectrometers.

Nevertheless, a majority of the ions generated in the ion source do notsurvive during transport from the source to the ion optics. Rather, themajority of the ions miss an entrance of the capillary tube, miss anentrance into the ion optics through a narrow orifice, and/or impinge onwalls of a capillary tube or nearby plates, and are lost. Thus, there isa need to increase the number of ions from an ambient pressure ionsource that are successfully transported through the capillary tube,reach the ion optics, and are transported into the mass spectrometer foranalysis.

SUMMARY

In a simple form, an interface for a mass spectrometer in accordancewith embodiments of the present invention includes an ion transfer tubehaving an inlet end opening to a high pressure chamber and an outlet endopening to a low pressure chamber. The high and low pressure chambersmay be provided by any regions that have respective higher and lowerpressures relative to each other. For example, the high pressure chambermay be an ion source chamber and the low pressure chamber may be a firstvacuum chamber. The ion transfer tube has at least one sidewallsurrounding an interior region and extending along a central axisbetween the inlet end and the outlet end. The ion transfer tube has aplurality of passageways formed in the sidewall. The passageways permitthe flow of gas from the interior region to a reduced-pressure regionexterior to the sidewall.

In another simple form, embodiments of the present invention include anion transfer tube for receiving and transporting ions from a source in ahigh pressure region to ion optics in a reduced pressure region of amass spectrometer. The ion transfer tube includes an inlet end, anoutlet end, and at least one sidewall surrounding an interior region andextending along a central axis between the inlet end and the outlet end.The ion transfer tube may also include an integral vacuum chamber tubeat least partially surrounding and connected to the ion transfer tube.The integral vacuum chamber tube isolates a volume immediatelysurrounding at least a portion of the ion transfer tube at a reducedpressure relative to the interior region. The sidewall has a structurethat provides at least one passageway formed in the sidewall. The atleast one passageway permits a flow of gas from the interior region tothe volume exterior to the sidewall. The structure and passageway areinside the integral vacuum chamber tube. The structure of the sidewallmay include a plurality of passageways.

In still another simple form, embodiments of the present inventioninclude a method of transporting ions from an ion source region to afirst vacuum chamber. The method includes admitting from the ion sourceregion, a mixture of ions and gas to an inlet end of an ion transfertube. The method also includes removing a portion of the gas through aplurality of passageways located intermediate the inlet end and anoutlet end of the ion transfer tube. The method further includes causingthe ions and the remaining gas to exit the ion transfer tube through theoutlet end into the first vacuum chamber. The method may also includesensing a reduction in latent heat in the ion transfer tube due to atleast one of removal of the portion of the background gas and anassociated evaporation, and increasing an amount of heat applied to theion transfer tube through a heater under software or firmware control.

The embodiments of the present invention have the advantage of reducedflow of gas through an exit end of the ion transfer tube. Severalassociated advantages have also been postulated. For example, thereduced flow through the exit end of the ion transfer tube decreases theenergy with which the ion bearing gas expands as it leaves the iontransfer tube. Thus, the ions have a greater chance of traveling on astraight line through an aperture of a skimmer immediately downstream.Also, reduction of the flow in at least a portion of the ion transfertube may have the effect of increasing the amount of laminar flow inthat portion of the ion transfer tube. Laminar flow is more stable sothat the ions can remain focused and travel in a straight line forpassage through the relatively small aperture of a skimmer. With gasbeing pumped out through a sidewall of the ion transfer tube, thepressure inside the ion transfer tube is reduced. Reduced pressure cancause increased desolvation. Furthermore, latent heat is removed whenthe gas is pumped out through the sidewall. Hence, more heat may betransferred through the ion transfer tube and into the sample remainingin the interior region resulting in increased desolvation and increasednumbers of ions actually reaching the ion optics.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of an example mass spectrometer with whichthe embodiments of the present invention may be incorporated.

FIG. 2 is a diagrammatic view of an inlet assembly in accordance with anembodiment of the present invention.

FIG. 3 is a diagrammatic view of an inlet assembly in accordance withanother embodiment of the present invention.

FIG. 4 is a diagrammatic partial perspective view of an ion transfertube in accordance with the embodiment of FIG. 3.

Like reference numerals refer to corresponding parts throughout theseveral views of the drawings.

DETAILED DESCRIPTION OF EMBODIMENTS

As has been discussed, conventional inlet sections having atmosphericpressure ionization sources suffer from a loss of a majority of the ionsproduced in the sources prior to the ions entering ion optics fortransport into filtering and analyzing sections of mass spectrometers.It is believed that high gas flow at an exit end of the ion transfertube is a contributing factor to this loss of high numbers of ions. Theneutral gas undergoes an energetic expansion as it leaves the iontransfer tube. The flow in this expansion region and for a distanceupstream in the ion transfer tube is typically turbulent in conventionalinlet sections. Thus, the ions born by the gas are focused only to alimited degree in the ion inlet sections of the past. Rather, many ofthe ions are energetically moved throughout a volume of the flowing gas.It is postulated that because of this energetic and turbulent flow andthe resultant mixing effect on the ions, the ions are not focused to adesirable degree and it is difficult to separate the ions from theneutral gas under these flow conditions. Thus, it is difficult toseparate out a majority of the ions and move them downstream while theneutral gas is pumped away. Rather, many of the ions are carried awaywith the neutral gas and are lost. On the other hand, the hypothesisassociated with embodiments of the present invention is that to theextent that the flow can be caused to be laminar along a greater portionof an ion transfer tube, the ions can be kept focused to a greaterdegree. One way to provide the desired laminar flow is to remove theneutral gas through a sidewall of the ion transfer tube so that the flowin an axial direction and flow out the exit end of the ion transfer tubeis reduced. Also, by pumping the neutral gas out of the sidewalls to amoderate degree, the boundary layer of the gas flowing axially insidethe ion transfer tube becomes thin, the velocity distribution becomesfuller, and the flow becomes more stable.

One way to increase the throughput of ions or transport efficiency inatmospheric pressure ionization interfaces is to increase theconductance by one or more of increasing an inner diameter of the iontransfer tube and decreasing a length of the ion transfer tube. As isknown generally, with wider and shorter ion transfer tubes, it will bepossible to transport more ions into the ion optics downstream. However,the capacity of available pumping systems limits how large the diameterand how great the overall conductance can be. Hence, in accordance withembodiments of the present invention, the inner diameter of the iontransfer tube can be made relatively large and at the same time flow outof the exit end of the ion transfer tube can be reduced to improve theflow characteristic for keeping ions focused toward a center of the gasstream. In this way, the neutral gas can be more readily separated fromthe ions, and the ions can be more consistently directed through theorifice of a skimmer into the ion optics and analyzer sectionsdownstream. The result is improved transport efficiency and increasedinstrument sensitivity.

Even if it is found in some or all cases, that turbulent flow results inincreased ion transport efficiency, it is to be understood thatdecreased pressure in a downstream end of the ion transfer tube andincreased desolvation due to the decreased pressure may be advantagesaccompanying the embodiments of the present invention under both laminarand turbulent flow conditions. Furthermore, even with turbulent flowconditions, the removal of at least some of the neutral gas through thesidewall of the ion transfer tube may function to effectively separatethe ions from the neutral gas. Even in turbulent flow, the droplets andions with their larger masses will most likely be distributed morecentrally during axial flow through the ion transfer tube. Thus, it isexpected that removal of the neutral gas through the sidewalls willeffectively separate the neutral gas from the ions with relatively fewion losses under both laminar and turbulent flow conditions. Stillfurther, the removal of latent heat by pumping the neutral gas throughthe sidewalls enables additional heating for increased desolvation underboth laminar and turbulent flow conditions.

Accordingly, FIG. 1 shows an example mass spectrometer 12 having an ionsource 15 in a source chamber 16 and an interface 18 between the highpressure source chamber 16 and a lower pressure first vacuum chamber 19.The ion source 15 may be, without limitation, an electrospray ionizationsource, a chemical ionization source, another liquid sample basedatmospheric pressure ionization source, or any other source. Theinterface 18 may include an ion transfer tube portion 21 and an ionguide portion 24 with separate or shared pumping stages. Ions from thesource 15 are introduced into the transfer tube portion 21 and movealong an ion path generally on a central axis 25 through one or moreadditional sections to a detector 27. The sections may include one ormore of each of ion guides, filters, collision cells, and analyzers, asindicated by q0, Q1, q2, and Q3. The devices in each of these sectionsmay be operated by an electronic controller 30 under software and/orfirmware control to perform the needed functions for analysis of sampleions in the mass spectrometer 12.

In the more detailed diagrammatic view of FIG. 2, a skimmer lens 33separates the ion transfer tube portion 21 from the ion guide portion 24of the interface 18. As shown, an ion transfer tube 36 may be supportednear its entrance end 39 on a chamber wall 42 between the source chamber16 and the first vacuum chamber 19. While FIG. 2 shows the ion transfertube 36 with an inlet or entrance end opening in direct communicationwith the ion source 15, it is to be understood that one or more reducedpressure chambers may be placed intermediate the ion source 15 and theion transfer tube 36. The one or more reduced pressure chambers may ormay not have one or more additional ion transfer tubes therein.

As shown in FIG. 2, sidewall 45 of the ion transfer tube extends axiallyfrom the entrance end 39 to an exit end 48 and is surrounded by a heater51. The heater 51 may be placed in direct contact or otherwise in anykind of thermal contact with the ion transfer tube 36. The skimmer lens33 may have an aperture positioned proximate to the outlet or exit end48 of the ion transfer tube 36. A tube lens or other focusing lens 52may be disposed between the exit end 48 of the ion transfer tube 36 andthe skimmer lens 33. An ion guide 54 may be located in a second vacuumchamber 57 downstream from the first vacuum chamber 19. It is to beunderstood that “vacuum chamber” as used herein may include any reducedpressure chamber or region that has a pressure that is lower thanatmospheric pressure. High pressure and low pressure as used hereindenote relative pressures in respective regions and are not to belimited to pressures relative to atmospheric or any other thresholdpressure. Each of the first and second vacuum chambers 19, 57 may bepumped by the same or separate vacuum pumps as indicated by arrows 58,59.

Alternatively, an interface 62 in accordance with another embodiment ofthe invention may include a third vacuum chamber 65 formed integrally asa unit with an ion transfer tube 68, as shown in FIG. 3. Walls create anenclosure that forms the third vacuum chamber 65 and at least partiallysurrounds an inner tube 71 that may be structurally analogous to the iontransfer tube 36 described with regard to the embodiment of FIG. 2above. As indicated by arrow 75, a separate pump or a pump in commonwith pump(s) of one or more of the first and second vacuum chambers 19,57 may be operably connected with the third vacuum chamber 65 in orderto pump gas from within an interior region 74 inside the ion transfertube 68 out through a sidewall 77 of the ion transfer tube 68. As withthe embodiment of FIG. 2, the sidewall 77 of the ion transfer tube 68extends axially from an entrance end 78 to an exit end 79. Also, thesidewall 77 is surrounded by a heater 51. The heater 51 may be placed indirect contact or otherwise in any kind of thermal contact with the iontransfer tube, as described with regard to the embodiment of FIG. 2.

FIG. 4 is a diagrammatic partial perspective view of the ion transfertube 68 of FIG. 3. As shown, the inner tube 71 and the interior region74 may be substantially the same as the ion transfer tube 36 and aninterior region thereof, in accordance with the embodiment of FIG. 2.The sidewall 77 has one or more passageways 80 for fluid communicationbetween the interior region 74 and an exterior region within theenclosure created by an enclosure sidewall 83 and enclosure end walls86, 87, which walls form the third vacuum chamber 65. As shown by arrows90, neutral gas is pumped from within the interior region 74 and outthrough the passageways 80 of the sidewall 77 into the third vacuumchamber 65 where it is pumped away. The third vacuum chamber 65encompasses a reduced-pressure region that is located within theenclosure and extends around the sidewall 77. As may be appreciated byreferring back to FIG. 3, the enclosure is disposed within the firstvacuum chamber 19 and communicates with a pump 91 that may be separateor in common with other pumps in the system.

Like the embodiment of FIGS. 3 and 4, the ion transfer tube 36 of theembodiment of FIG. 2 may have similar structure in which the sidewall 45has passageways 80, and the neutral gas is pumped away by a pump influid communication with the first vacuum chamber 19. As shown in FIG.4, a sensor 93 may be connected to the ion transfer tube 68 and to thecontroller 30 for sending a signal indicating a temperature of thesidewall 77 or some part of the ion transfer tube 68 back to thecontroller 30. It is to be understood that a plurality of sensors may beplaced at different positions to obtain a temperature profile. Thus, thesensor(s) 93 may thus be connected to the ion transfer tube 68 fordetecting a reduction in heat as gas is pumped through the plurality ofpassageways 80 in the sidewall 77 of the ion transfer tube 68. Thesensor(s) 93 may also be connected to the ion transfer tube 36 andcontroller 51 in the embodiment of FIG. 2 for heat reduction detectionand control.

With further reference to the embodiment of FIGS. 3 and 4, the thirdvacuum chamber 65 may be utilized to introduce a flow of gas through thesidewall 71 and into an interior region 74 of the ion transfer tube 68instead of removing the background gas, as described above. This may beachieved by adjusting the pressure in the third chamber 65 to be betweenatmospheric pressure and the pressure in the interior region 74. Byintroducing a flow of gas through passageways 80 into the interiorregion 74, more turbulent flow conditions may be created in which sampledroplets are disrupted. The more turbulent flow conditions may thuscause the sample droplets to be broken up into smaller droplets. Thisdisruption of the droplets is an external force disruption, as opposedto a coulomb explosion type disruption which also breaks up thedroplets.

In an application of both external force and coulomb explosiondisruption, both removal and addition of gas may be applied in one iontransfer tube. For example, the chamber 65 could be divided into pluralregions with respective removal and addition of gas in a series of theplural regions. Thus, an alternating series of external force andcoulomb explosion disruptions can be implemented to break up thedroplets of the sample.

The sidewall 45 of the ion transfer tube 36 and the sidewall 77 thatforms at least a part of the inner tube 71 in the embodiments of FIGS.1-4 may be formed from a material that includes one or more of a metalfrit, a metal sponge, a permeable ceramic, and a permeable polymer. Thepassageways 80 may be defined by the pores or interstitial spaces in thematerial. The pores or interstices in the material of the sidewalls maybe small and may form a generally continuous permeable element withoutdiscrete apertures. Alternatively, the passageways may take the form ofdiscrete apertures or perforations formed in the sidewalls 45, 77 of iontransfer tubes 36, 68. The passageways may be configured by throughopenings that have one or more of round, rectilinear, elongate, uniform,and non-uniform configurations.

Embodiments of the present invention include a method of transportingions from a source region into a vacuum region, a method of separatingand removing a background gas from a mixture of the background gas andsample ions, and a method of desolvating a sample in an interface. Oneor more of the methods may include heating the ion transfer tube topromote evaporation of residual liquid solvent admitted into the iontransfer tube. The methods may include the step of removing at least aportion of the gas by providing a reduced-pressure region exterior to aninner tube of the ion transfer tube. The methods may also includesensing a reduction in latent heat in the ion transfer tube due to atleast one of removal of the portion of the background gas and anassociated evaporation. A subsequent step to sensing may be the step ofincreasing an amount of heat applied to the ion transfer tube through aheater under software or firmware control.

The methods may include reducing a pressure in at least a portion of theion transfer tube interior region such that desolvation is increased.The methods may include reducing the energy of a free jet expansion ofthe gas leaving the outlet or exit end of the ion transfer tube. Themethods may also include reducing a velocity of a second downstreamportion of the background gas that moves axially out an outlet or exitend of the ion transfer tube relative to a velocity of a first upstreamportion of the background gas entering the ion transfer tube. The methodmay also include increasing a proportion of laminar flow along a lengthof the ion transfer tube.

The embodiments and examples set forth herein were presented in order tobest explain the present invention and its practical application and tothereby enable those of ordinary skill in the art to make and use theinvention. However, those of ordinary skill in the art will recognizethat the foregoing description and examples have been presented for thepurposes of illustration and example only. The description as set forthis not intended to be exhaustive or to limit the invention to theprecise form disclosed. Many modifications and variations are possiblein light of the teachings above without departing from the spirit andscope of the forthcoming claims.

1. An interface for a mass spectrometer, comprising: an ion transfertube having an inlet end opening to an atmospheric pressure chamber, anoutlet end opening to a low pressure chamber, and at least one sidewallsurrounding an interior region through which is directed a flow of gasand ions, the sidewall extending along a central axis between the inletend and the outlet end; at least a portion of the sidewall beingfabricated from a porous material to permit the flow of gas from theinterior region through the sidewall to a reduced-pressure regionexterior to the sidewall.
 2. The interface of claim 1, wherein theatmospheric pressure chamber comprises an ion source chamber, and thelow pressure chamber comprises a first vacuum chamber.
 3. The interfaceof claim 2, wherein the ion source chamber is configured as anelectrospray ionization source.
 4. The interface of claim 2, wherein theion source chamber is configured as a chemical ionization source.
 5. Theinterface of claim 2, wherein the reduced-pressure region is locatedwithin an enclosure extending around the sidewall, the enclosure beingdisposed within the first vacuum chamber and communicating with a pump.6. The interface of claim 1, further comprising a heater in thermalcontact with the ion transfer tube.
 7. The interface of claim 1, whereinthe porous material is at least one of a a permeable ceramic, or apermeable polymer.
 8. The interface of claim 1, wherein the porousmaterial is a porous metal.
 9. The interface of claim 1, furthercomprising a skimmer lens having an aperture positioned proximate to theoutlet end. 10-17. (canceled)